Sepsis and septic shock represent the most common cause of death in ICU patients. The most characteristic hemodynamic finding in septic shock patients is a decreased systemic vascular resistance (SVR). The cause of this decreased SVR is not known; however, complement activation with production of C5a may be involved. C5a is a known anaphylotoxin that can cause mast cells to release vasoactive mediators. Serial serum samples for C5a and other complement components were drawn from patients with septic shock and correlated with simultaneous hemodynamic determinations. Serum C5a was found to be abnormal more commonly than other complement components in these patients. C5a was found to be abnormal in patients with blood culture positive septic shock and blood culture negative septic shock; it was never elevated in hypovolemic or cardiogenic shock. The elevated serum C5a levels significantly correlated (negatively) with systemic vascular resistance index, indicating a possible role for the known anaphylotoxin C5a in the complex pathogenesis of septic shock.